Universal Assay for Methyltransferases.

The overarching goal of this proposal is to improve upon the current assays that monitor SAdenosylmethionine dependent enzymes and ATP dependent enzymesATP and S adenosylmethionineAdoMetare the two most common substrates in all living organismsHaving recently shown that the bacterial enzyme Methylthioadenosine NucleosidaseMTANcan readily bind the productsADP and S adenosylhomocysteinederived from enzymatic reactions using either of these substrateswe propose to engineer new variants of this enzyme to improve affinity to these compoundsThese variants will form the basis for mix and readcontinuous assays that can be coupled to any ATP or AdoMet utilizing enzymeThe first portion of the study will make MTAN variants and test them for binding to either AdoMet or AdoHcy to assess affinityIn the second aimother MTAN variants will be made and affinity to ATPADPand AMP will be testedIt is expected that results obtained from this study will product two marketable products for in vitro enzymatic testingone for AdoMet dependent enzymes and one for ATP dependent enzymes Project Narrative Drug discovery efforts that lead to new treatments for CancerHeart DiseaseInfectious Diseasesand countless other human ailments focus on identifying and optimizing compounds that inhibit enzyme functionThis research aims to develop more sensitive and more rapid tools for identifying and testing potential drugs